首页|LncRNA-XIST通过抑制miR-186-5p上调PSME3表达促进急性骨髓性白血病发展的机制研究

LncRNA-XIST通过抑制miR-186-5p上调PSME3表达促进急性骨髓性白血病发展的机制研究

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目的 探讨长链非编码RNA X染色体失活特异性转录因子(long noncoding RNA X-inactive specific transcript,lncRNA-XIST)通过抑制miR-186-5p上调PSME3 表达促进急性骨髓性白血病发展的分子机制。方法 采用生存曲线(Kaplan-Meier曲线)生存分析XIST表达对32 例急性骨髓性白血病儿童患者生存率的影响,miRNA模拟物、miRNA抑制剂、PSME3 shRNA转染KG-1 细胞后,RT-qPCR检测XIST及miR-186-5p mRNA表达水平,Western-blotting检测PSME3、cleaved-caspase 3 及cleaved-caspase 8 的表达水平,CCK-8 及细胞凋亡实验检测KG-1 细胞的活力。结果 XIST在急性骨髓性白血病儿童患者临床样本及细胞系中显著表达。在KG-1 细胞中,敲降XIST抑制细胞的增殖,并诱导凋亡。敲降XIST的KG-1 细胞移植瘤小鼠肿瘤体积及重量显著低于对照组。双荧光素酶报告基因检测结果显示miR-186-5p与XIST相互作用,机制研究发现XIST通过内源性竞争海绵吸附miR-186-5p影响其下游靶基因PSME3 的表达。结论 XIST在急性骨髓性白血病中可通过海绵吸附miR-186-5p调控PSME3 表达,XIST的异常表达可作为急性骨髓性白血病诊断及治疗的作用靶点。
Promotion of acute myeloid leukemia progression by lncRNA-XIST via suppression of miR-186-5p and up-regulation of PSME3 expression
Objective To investigate the mechanism of long intergenic noncoding RNA X-inactive specific transcript(lncRNA-XIST)promoted acute myeloid leukemia(AML)progression by suppressing miR-186-5p.Methods Kaplan-meier was used to analyze the correlation between XIST expression and survival in 32 AML patients.KG-1 cells were tranfected with miRNA mimic,miRNA inhibitor or PSME3 shRNAs.Subsequently,the mRNA expression levels of XIST and miR-186-5p were detected by quantitative real-time PCR.The protein expression levels of PSME3,cleaved-caspase 3 and cleaved-caspase 8 were detected by Western-blotting.Cell viability detected by CCK-8 assay and flow cytometry.Results XIST were significantly expressedby AML patients and AML cell lines.Knocking down XIST inhibited the proliferation and promoted the apoptosis of KG-1 cells.Moreover,when KG-1 cells with XIST knockdown were transplanted into nude mice,tumor formation and progression were remarkably suppressed.Dual-luciferase reporter assay showed that miR-186-5p targeted XIST.The mechanism investigation showd that XIST endogenously competed sponge miR-186-5p regulate PSME3 expression.Conclusion XIST endogenously competed as a sponge for miR-186-5p to regulate PSME3 expression in AML,and the aberrant expression of XIST is a potential molecular target for AML diagnosis and therapy.

acute myeloid leukemiaXISTmiR-186-5pPSME3

曲海燕、姜友章、杨国鹏、孙允霄

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滨州医学院烟台附属医院 儿科,山东 烟台 264100

急性骨髓性白血病 XIST miR-186-5p PSME3

2024

沈阳药科大学学报
沈阳药科大学

沈阳药科大学学报

CSTPCD
影响因子:0.604
ISSN:1006-2858
年,卷(期):2024.41(12)